During healthy muscle development, myoblasts (generally, primordial muscle cells) may proliferate and/or differentiate and then fuse to form multi-nucleated fibers called myotubes. Mature or adult-like myotubes are generally highly multinucleated and are relatively thick and long, particularly when compared to immature myotubes. Mature myotubes also may form branched structures and typically have a central core occupied by nuclei and sarcoplasm, which may give the cells a tubular appearance. Interestingly, mature myotubes in vivo tend to be highly adaptable in response to changes in physiological demands or in response to disease and are able to undergo phenotypic changes in size (hypertrophy or atrophy) and in metabolic capacity (e.g., ranging from relying on highly oxidative pathways to highly glycolytic pathways).
Muscle fibers in vivo may also appear as slow-twitch or fast-twitch forms. Slow-twitch fibers tend to rely on aerobic respiration (glycolysis and Krebs cycle) to fuel muscle contraction and are ideal for long-term endurance (e.g., long-distance running) and for postural support. Slow-twitch fibers generally have relatively high oxygen requirements and generally have high numbers of mitochondria and high concentrations of myoglobin, an oxygen-binding protein found in the blood that gives muscles their reddish color. In contrast, fast-twitch fibers tend to rely on anaerobic respiration (glycolysis alone) to fuel muscle contraction and are ideal for quick contractions of short duration and are useful for rapid bursts of movement.
Muscular diseases and disorders, both developmental and degenerative, can cause the gradual or sudden loss of muscular function due to the decline or death of muscle cells, as well as lessened muscular development due to developmental diseases. Congenital myopathies are examples of muscular diseases that present these characteristics. Muscle loss may also occur from aging, from the treatment of diseases, or from a number of other causes. Examples of these types of muscle loss include sarcopenia and cachexia. There is a need in the art for therapies for the various types of muscle loss.